Bicalutamide represented by the formula (I):
is useful as a compound having an antiandrogenic activity.
Regarding a production method of bicalutamide, various methods have been known in JP-2005-60302A and the like, and N-methacryloyl-4-cyano-3-trifluoromethylaniline which is obtainable from 4-cyano-3-trifluoromethylaniline represented by the formula (II):
is generally used as a raw material.
For example, JP-2005-60302A discloses a method for producing N-methacryloyl-4-cyano-3-trifluoromethylaniline by reacting 4-cyano-3-trifluoromethylaniline with methacryloyl chloride. Further, EP-365763A discloses a preparation method of crystallizing 4-cyano-3-trifluoromethylaniline in ethanol/water.
When, N-methacryloyl-4-cyano-3-trifluoromethylaniline was produced from 4-cyano-3-trifluoromethylaniline industrially in a large scale according to the method described in JP-2005-60302A, a defect in a liquid separation property was observed in steps of extracting N-methacryloyl-4-cyano-3-trifluoromethylaniline from a reaction solution and washing the extract. This defect in the liquid separation property was not easily improved with change in extraction and washing methods.